Different expression of calreticulin and immunoglobulin binding protein in Alzheimer's disease brain

Abstract

Both calreticulin (CRT) and immunoglobulin binding protein (Bip) have a role in the folding and assembly of oligomeric membrane proteins in the endoplasmic reticulum (ER). Recent studies have demonstrated the generation of beta-amyloid protein (Abeta) 1-42, a key peptide for amyloid deposits, in the ER. We, therefore, examined the localization and expression of CRT, Bip and their mRNA by immunohistochemistry, Western blot, in situ hybridization and semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in both neurologically normal and Alzheimer's disease (AD) brains. Two polyclonal anti-CRT antibodies gave similar positive staining of CRT in neurons and glia. In neuronal cells, the cytoplasm, nucleoli and their processes were positive for CRT. In glial cells, perinuclear staining was frequently seen and the processes of some glial cells were also stained. In AD, these antibodies stained clearly damaged neurons but the number and the intensity of positive cells were decreased compared to controls. Processes of microglial cells were markedly positive in the AD white matter. Western blots using an anti-CRT antibody showed significantly lower immunoreactive bands in AD than control brains. By in situ hybridization, the number of neurons which express the CRT mRNA was less in AD than in controls. Using RT-PCR, the relative levels of the CRT mRNA in AD brains were also found to be significantly lower than those in controls. On the other hand, the number of Bip-positive cell, the production of Bip and the expression of mRNA for Bip did not differ between control and AD brains. These results suggest that CRT may be a multifunctional protein in human brain, and that the weak expression of CRT and the positive staining of microglial processes in AD brain may be part of the pathological processes in AD.

Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS

“…In particular, laser-captured motoneurons from presymptomatic mSOD1 mice showed a 30% decrease in CRT mRNA (Perrin et al, 2005) and reduced CRT protein levels are apparent in symptomatic mSOD1 spinal cord (Teuling et al, 2007). Moreover, CRT is downregulated in cortical neurons of Alzheimer's patient brains (Taguchi et al, 2000) and in striatal neurons of hemiparkinsonian rats (Lessner et al, 2010). Although no functional studies were carried out, it is striking that ER stress is activated in all the above contexts (Wang and Takahashi, 2007;Lee et al, 2010;Lessner et al, 2010).…”

Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

“…Calreticulin (CRT) can also function as a cC1q receptor. Its expression, mainly in processes of microglia, is weak in AD brain, compared to control brain [164]. CRT is primarily localized to the ER, and involved in regulation of Ca2+ homeostasis and as chaperone for nascent proteins.…”

“…In AD brain, CRT can be found in damaged neurons [164]. The majority of MAP-2 positive rat cortical neurons is CRT positive and able to bind C1q in a saturable fashion in vitro.…”

Cell Line Dependent RNA Expression Profiles of Prion-infected Mouse Neuronal Cells

“…51 Calreticulin is involved in the proper folding of proteins in the endoplasmic reticulum 52 and has been demonstrated to be down-regulated in AD. 53 Its up-regulation in prion-infected GT1 cells may be a response to the production of misfolded prion proteins. Fibronectin is also up-regulated in AD and ScGT1.…”